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Title: Regulator of G protein signaling 18 regulates megakaryopoiesis and the cilia-mediated vertebrate mechanosensory system
Authors: Louwette, Sophie
Thys, Chantal
Wittevrongel, Christine
Labarque, Veerle
Gijsbers, Rik
Debyser, Zeger
Van Geet, Chris
Freson, Kathleen #
Issue Date: Jul-2011
Publisher: Blackwell Pub.
Series Title: Journal of Thrombosis and Haemostasis
Conference: ISTH location:kyoto date:july 2011
Abstract: RGS18 was originally identified as member of the R4 subfamily of regulators of G protein signalling (RGS) to act as GTPase-activating protein and with specific expression in haematopoietic progenitors, myeloerythroid cells and megakaryocytes. The role of RGS18 in haematopoiesis and megakaryopoiesis however remained unknown. We here showed that lentiviral RGS18 overexpression in Sca1+ hematopoietic mice stem cells increased megakaryocyte proliferation. Flow cytometric analysis revealed a significantly higher amount of CD41/61-positive megakaryocytes after transduction with LV-GFP/T2A/RGS18 compared to LV-GFP/T2A/RGS18del. In addition, morpholino (MO) mediated RGS18 depletion in Danio rerio resulted in thrombocytopenia without defects in early hematopoiesis, erythrocytes or macrophages. Injection of the three MOs individually resulted in a reduction in the number of GFP-labeled thrombocytes as quatified by live screening, flow cytometry and immunoblot. Moreover this study also revealed that RGS18 function was not restricted to hematopoiesis as RGS18 depleted embryos present with curly tails, a delay in blood vessel development and deafness. In situ hybridization in Danio rerio, Xenopus laevis and mouse showed RGS18 expression not only in thrombocytes and/or hematological tissues but also in the developing brain and ear. RGS18 was shown to interfere with cilia development in hear cells of the inner ear and with the migration of neuromast cells that consist of hair cells with cilia. We further showed that spinophilin, as binding partner for RGS18, was also strongly decreased after RGS18 depletion. In conclusion, this study was the first to illustrate a functional role for RGS18 in megakaryopoiesis and revealed its unexpected role in ciliogenesis.
Publication status: published
KU Leuven publication type: IMa
Appears in Collections:Faculty of Medicine @ Kulak
Molecular Virology and Gene Therapy
Department of Cardiovascular Sciences - miscellaneous
Molecular and Vascular Biology
# (joint) last author

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